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Case Reports
. 2020 Apr 30:4:PO.19.00258.
doi: 10.1200/PO.19.00258. eCollection 2020.

Sustained Complete Response to Palbociclib in a Refractory Pediatric Sarcoma With BCOR- CCNB3 Fusion and Germline CDKN2B Variant

Timothy F Tramontana  1 , Mark S Marshall  2 , Amy E Helvie  2 , Morgan R Schmitt  2 , Jennifer Ivanovich  1 , Jacquelyn L Carter  2 , Jamie L Renbarger  2 , Michael J Ferguson  2
Affiliations
Case Reports

Sustained Complete Response to Palbociclib in a Refractory Pediatric Sarcoma With BCOR- CCNB3 Fusion and Germline CDKN2B Variant

Timothy F Tramontana et al. JCO Precis Oncol. .
No abstract available

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Michael J. FergusonConsulting or Advisory Role: Bayer No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Patient timeline and response imaging. (A) The timeline of treatments and disease recurrences and progression in our patient. Red circles represent time of recurrence or progression. Hash marks represent prolonged period of time progressed through therapy (not to scale of remaining timeline). Patient is still continuing with palbociclib therapy after the most recent scans in March 2019. (B) Patient imaging displayed with initial diagnostic magnetic resonance imaging from 2010; subsequent relapse scans were done via computed tomography imaging. Red lines outline tumor boundaries. There was concern for progression after 2 cycles of palbociclib, but there was a 2-month lag between the “before palbociclib” scan and actually starting drug, so interval progression likely occurred in this timeframe. No new baseline scan was performed on the day palbociclib started. Each cycle of palbociclib was 28 days. NED, no evidence of disease.
FIG 2.
FIG 2.
Transcriptome analysis reveals activation of the cyclin-dependent kinase 4/6 (CDK4/6)-RB pathway. (A) Circos plot of patient’s tumor genome. (B) Identification of BCOR-CCNB3 fusion. This graphic illustrates the fusion of BCOR exon 15 to CCNB3 exon 5. With the exception of the destruction box in CCNB3, all functional domains from each encoded protein remain intact in the BCOR-CCNB3 fusion protein. (C) The CDK4/6 pathway is a gene regulatory program controlled by multiple tiers of protein kinases and transcriptional regulators. Increases in cyclin-D or CDK4 or 6 protein can lead to phosphorylation of the RB1-E2F tumor suppressor complex. Upon phosphorylation of RB1, the E2F1-3 transcription factors are released from the complex and are able to bind to the promoters of target genes, driving activation of transcription. These target genes include E2F1-3 themselves, the CDC25 genes, TOP2A, BUB1, and BUB1B. WT, wild type.
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References

    1. Whang-Peng J, Triche TJ, Knutsen T, et al. Cytogenetic characterization of selected small round cell tumors of childhood. Cancer Genet Cytogenet. 1986;21:185–208. - PubMed
    1. Turc-Carel C, Aurias A, Mugneret F, et al. Chromosomes in Ewing’s sarcoma: I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12) Cancer Genet Cytogenet. 1988;32:229–238. - PubMed
    1. Ginsberg JP, de Alava E, Ladanyi M, et al. EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing’s sarcoma. J Clin Oncol. 1999;17:1809–1814. - PubMed
    1. Shing DC, McMullan DJ, Roberts P, et al. FUS/ERG gene fusions in Ewing’s tumors. Cancer Res. 2003;63:4568–4576. - PubMed
    1. Pierron G, Tirode F, Lucchesi C, et al. A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion. Nat Genet. 2012;44:461–466. - PubMed

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